The goal of our investigation is to identify and to solve immunological problems in fetal pancreas transplantation in allogeneic recipients. The studies in the genetically defined rat model will include: (1) to attempt to suppress host immunereaction against donor antigens by specific immunotherapies to prolong fetal pancreas allograft survivals. An induction of specific unresponsiveness to donor antigens (suppressor T-cell mediated) and specific immunosuppression by active or passive enhancement will be tested in various donor-recipient combinations, (2) to verify the use of nude mice as an in vivo culture system for xenogenic fetal pancreases by comparing growth and development of fetal pancreases cultured in nude mice to those cultured in syngeneic recipients, (3) to identify effect of anti-insulin antibodies or autoimmunity to islet cells on allograft functions, and (4) to monitor tumor incidence in long surviving fetal pancreas recipients. We believe that the proposed investigation is an essential step to proceed in our investigation to demonstrate the feasibility of fetal pancreas transplants for reversal of Diabetes in human beings.